Gastrointestinal Kaposi sarcoma (KS) is classical, but rare. The AKT signaling pathway plays a central role in G protein-coupled receptor, key protein of KS histogenesis, encoded by KSHV/HHV8. There is increasing evidence that rapamycin, acting on AKT pathway, may be useful in the treatment of KS, including in HIV patients. We aimed to study the expression pattern of AKT pathway proteins in gastrointestinal KS. Expression of AKT, 4EBP1, PTEN, mTOR was assessed in 19 gastrointestinal KS biopsies by immunohistochemistry (17 patients). Protein expression in tumor spindle cells and in intratumor stromal vascular endothelial cells was analyzed with regard to clinicomorphological features. Tumor AKT related to lack of marked extravasated erythrocytes, tumor PTEN to presence of intratumor hemosiderin (p = 0.04 for both comparisons). Presence of both extravasated erythrocytes and hemosiderin related directly to endothelial stromal vascular nuclear PTEN and to low endothelial mTOR (p = 0.4 and 0.03, respectively). High tumor 4EBP1 related to a high slit-type abnormal vascular component (p = 0.04). The results of our study suggest pro-permeability or pro-angiogenic roles for 4EBP1 and PTEN and, opposite roles for AKT and mTOR in KS. Our hypotheses warrant further studies to obtain more generally applicable results.